Oxidative Stress andβ-Thalassemic Erythroid Cells behind the Molecular Defect

Abstract

β-thalassemia is a worldwide distributed monogenic red cell disorder, characterized by the absence or reducedβ-globin chain synthesis. Despite the extensive knowledge of the molecular defects causingβ-thalassemia, less is known about the mechanisms responsible for the associated ineffective erythropoiesis and reduced red cell survival, which sustain anemia ofβ-thalassemia. The unbalance of alpha-gamma chain and the presence of pathological free iron promote a severe red cell membrane oxidative stress, which results in abnormalβ-thalassemic red cell features. These cells are precociously removed by the macrophage system through two mechanisms: the removal of phosphatidylserine positive cells and through the natural occurring antibody produced against the abnormally clustered membrane protein band 3. In the present review we will discuss the changes inβ-thalassemic red cell homeostasis related to the oxidative stress and its connection with production of microparticles and with malaria infection. The reactive oxygen species (ROS) are also involved in ineffective erythropoiesis ofβ-thalassemia through still partially known pathways. Novel cytoprotective systems such as ASHP, eIF2α, and peroxiredoxin-2 have been suggested to be important against ROS inβ-thalassemic erythropoiesis. Finally, we will discuss the results of the majorin vitroandin vivostudies with antioxidants inβ-thalassemia.